Genetic data from the extinct giant rat from Tenerife (Canary Islands) points to a recent divergence from mainland relatives

Evolution of vertebrate endemics in oceanic islands follows a predictable pattern, known as the island rule, according to which gigantism arises in originally small-sized species and dwarfism in large ones. Species of extinct insular giant rodents are known from all over the world. In the Canary Islands, two examples of giant rats, †Canariomys bravoi and †Canariomys tamarani, endemic to Tenerife and Gran Canaria, respectively, disappeared soon after human settlement. The highly derived morphological features of these insular endemic rodents hamper the reconstruction of their evolutionary histories. We have retrieved partial nuclear and mitochondrial data from †C. bravoi and used this information to explore its evolutionary affinities. The resulting dated phylogeny confidently places †C. bravoi within the African grass rat clade (Arvicanthis niloticus). The estimated divergence time, 650 000 years ago (95% higher posterior densities: 373 000–944 000), points toward an island colonization during the Günz–Mindel interglacial stage. †Canariomys bravoi ancestors would have reached the island via passive rafting and then underwent a yearly increase of mean body mass calculated between 0.0015 g and 0.0023 g; this corresponds to fast evolutionary rates (in darwins (d), ranging from 7.09 d to 2.78 d) that are well above those observed for non-insular mammals.     

Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling.

We describe genetic screens in Saccharomyces cerevisiae designed to identify mammalian nonreceptor modulators of G-protein signaling pathways. Strains lacking a pheromone-responsive G-protein coupled receptor and expressing a mammalian-yeast Galpha hybrid protein were made conditional for growth upon either pheromone pathway activation (activator screen) or pheromone pathway inactivation (inhibitor screen). Mammalian cDNAs that conferred plasmid-dependent growth under restrictive conditions were identified. One of the cDNAs identified from the activator screen, a human Ras-related G protein that we term AGS1 (for activator of G-protein signaling), appears to function by facilitating guanosine triphosphate (GTP) exchange on the heterotrimeric Galpha. A cDNA product identified from the inhibitor screen encodes a previously identified regulator of G-protein signaling, human RGS5.     

Specification of the direction of adhesive signaling by the integrin beta cytoplasmic domain

Integrin adhesion receptors can signal in two directions: first, they can regulate cellular behaviors by modulating cellular signaling enzymes ("outside-in signaling"); second, cells can regulate the affinity of integrins ("inside-out signaling") by such pathways. Integrin beta cytoplasmic domains (tails) mediate both types of signaling, and Src family kinases (SFKs) and talin, which bind to beta tails, are important for integrin signaling. Here, we utilized "homology scanning" mutagenesis to identify beta tail mutants selectively defective in c-Src binding and found that amino acid exchanges affecting a combination of an Arg and Thr residue in the integrin beta3 tail control the binding specificity for SFKs but have no effect on talin binding. Using beta tail mutants at these residues, we found that SFK binding to integrin beta tails is dispensable for inside-out signaling but is obligatory for cell spreading, a marker of outside-in signaling. Conversely, we found that point mutations that disrupt talin binding abolish integrin activation, but they do not inhibit SFK binding to the beta3 tail or the initiation of outside-in signaling once the integrins are in a high affinity form. Thus, we show that inside-out and outside-in integrin signaling are mediated by distinct and separable interactions of the integrin beta tails. Furthermore, based on our results, it is possible to discern the relative contributions of the direction of integrin signaling on biological functions in cell culture and, ultimately, in vivo.     

Mangrove characterization of Central America with remote sensors

Satellite images were used to study the mangrove distribution patterns in two different climatic regions of Central America: Gulf of Fonseca in Honduras-El Salvador and Sierpe-Térraba in Costa Rica. The Gulf of Fonseca has higher temperature and solar radiation, and lower precipitation, which can explain the higher structural development and species mixing of the Sierpe-Térraba mangrove. In the latter the transition between species or between heights in the same species is clear. The automatic classification made by the Geographic Information System (IDRISI) fits well the field mangrove distribution, but it was necessary to regroup some subdivisions that represent the same land use as identified by transects and an aerial video. Mixed species and clouds produced less satisfactory results in Sierpe-Térraba indicating a need for better satellite image resolution.     

MicroRNA expression profiling in blood from fragile X‐associated tremor/ataxia syndrome patients

Fragile X‐associated tremor/ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder associated with FMR1 gene premutation alleles (55–200 CGG repeats). Fragile X‐associated tremor/ataxia syndrome clinical core features include action tremor, gait ataxia, cognitive deficits progressing to dementia, and frequently parkinsonism. Although the pathogenic molecular mechanism of FXTAS is not completely understood, the restriction of the phenotype to the FMR1 premutation range has given rise to a model based on a RNA toxic gain‐of‐function. Since the identification of the first microRNAs (miRNAs) and their role in normal development, several studies have associated them with neurodegenerative diseases such as Parkinson, Alzheimer and Huntington diseases, suggesting that they play a key role in brain development, as well as in its morphogenesis. Herein, we present the characterization of miRNA expression profiles in FXTAS male patients using deep sequencing‐based technologies and microarray technology. Deep sequencing analysis evidenced 83 miRNAs that were significantly deregulated whereas microarray analysis showed 31. When comparing these results, 14 miRNAs were found deregulated in FXTAS patients. MiR‐424 and miR‐574‐3p showed significant fold change adjusted P‐values in both platforms in FXTAS patients. MiR‐424 has been founded substantially and specifically enriched in human cerebral cortical white matter of Alzheimer disease patients, which, together with cerebral atrophy, is a prominent imaging finding in individuals with FXTAS. The study provides the first systematic evidence of differential miRNA expression changes in FXTAS blood samples. Although further studies are necessary to better characterize the miRNA function in FXTAS disorder, our results suggest that they might contribute to its pathogenesis.